+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

An epigenetic auto-feedback loop regulates TGF-β type II receptor expression and function in NSCLC



An epigenetic auto-feedback loop regulates TGF-β type II receptor expression and function in NSCLC



Oncotarget 6(32): 33237-33252



The downregulation of transforming growth factor-β (TGF-β) type II receptor (TβRII) expression and function plays a pivotal role in the loss of the TGF-β-induced tumor suppressor function that contributes to lung cancer progression. The aberrant expression of miRNAs has been shown to be involved in the regulation of oncogenes and tumor suppressor genes. Our current study involving miRNA microarray, northern blot and QRT-PCR analysis shows an inverse correlation between miR-20a and TβRII expression in non-small cell lung cancer (NSCLC) tissues and cell lines. Stable expression of miR-20a downregulates TβRII in lung epithelial cells which results in an inhibition of TGF-β signaling and attenuation of TGF-β-induced cell growth suppression and apoptosis. Stable knock down of miR-20a increases TβRII expression and inhibits tumorigenicity of lung cancer cells in vivo. Oncogene c-Myc promotes miR-20a expression by activating its promoter leading to downregulation of TβRII expression and TGF-ß signaling. MiR-145, which is upregulated by TGF-β, inhibits miR-20a expression by targeting c-Myc and upregulates TβRII expression. These correlations among miRNAs and cellular proteins are supported by TCGA public database using NSCLC specimens. These results suggest a novel mechanism for the loss of TβRII expression and TGF-β-induced tumor suppressor functions in lung cancer through a complex auto-feedback loop TGF-β/miR-145/c-Myc/miR-20a/TβRII.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 057179809

Download citation: RISBibTeXText

PMID: 26356817

DOI: 10.18632/oncotarget.4893


Related references

Androgen receptor auto-regulates its expression by a negative feedback loop through upregulation of IFI16 protein. Febs Letters 580(6): 1659-1664, 2006

Myostatin auto-regulates its expression by feedback loop through Smad7 dependent mechanism. Journal of Cellular Physiology 206(1): 264-272, 2006

Epigenetic control of a VDR-governed feed-forward loop that regulates p21(waf1/cip1) expression and function in non-malignant prostate cells. Nucleic Acids Research 39(6): 2045-2056, 2011

Nitric Oxide-Dependent Feedback Loop Regulates Transient Receptor Potential Vanilloid 4 (TRPV4) Channel Cooperativity and Endothelial Function in Small Pulmonary Arteries. Journal of the American Heart Association 6(12):, 2017

A positive feedback loop that regulates cyclooxygenase-2 expression and prostaglandin F2alpha synthesis via the F-series-prostanoid receptor and extracellular signal-regulated kinase 1/2 signaling pathway. Endocrinology 146(11): 4657-4664, 2005

The EGF receptor-sox2-EGF receptor feedback loop positively regulates the self-renewal of neural precursor cells. Stem Cells 28(2): 279-286, 2010

Platelet-activating factor (PAF) positively auto-regulates the expression of human PAF receptor transcript 1 (leukocyte-type) through NF-kappa B. Biochemical and Biophysical Research Communications 205(2): 1137-1142, 1994

Let-7 regulates Dicer expression and constitutes a negative feedback loop. Carcinogenesis 29(11): 2073-2077, 2008

Ultraviolet uv light regulates human keratinocyte kc tumor necrosis factor receptor tnfr expression and function via an autocrine loop. Journal of Investigative Dermatology 98(4): 563, 1992

A negative feedback loop at the nuclear periphery regulates GAL gene expression. Molecular Biology of the Cell 23(7): 1367-1375, 2012

The exosome regulates circadian gene expression in a posttranscriptional negative feedback loop. Cell 138(6): 1236-1246, 2009

PIL1 participates in a negative feedback loop that regulates its own gene expression in response to shade. Molecular Plant 7(10): 1582-1585, 2014

P53 Regulates the Expression of LRP1 and Apoptosis through a Stress Intensity-Dependent MicroRNA Feedback Loop. Cell Reports 24(6): 1484-1495, 2018

Intronic promoter-mediated feedback loop regulates bean PvSR2 gene expression. Biochemical and Biophysical Research Communications 463(4): 1097-1101, 2015

Twist Regulates Cytokine Gene Expression through a Negative Feedback Loop that Represses NF-kB Activity. Cell 112(2): 9-80, 2003